The introduction of antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection into a chronic disease. Pulmonary arterial hypertension (PAH) in HIV is an important cause of morbidity and mortality is thought to have the the worst prognosis of any subtype of PAH with presenting symptoms often including dyspnea and exercise limitation (ExLT), commonly attributed to other disorders. In this grant application, we propose a prospective study to understand the cardiopulmonary responses and PAH in HIV using echocardiography in conjunction with exercise magnetic resonance imaging (MRI) and cardiopulmonary testing. We further propose innovative assessment of inflammatory parameters in HIV that will provide insights into the mechanisms of cardiopulmonary dysfunction and elevated PA pressures. Our hypothesis is that HIV- ExLT patients commonly exhibit alteration in RV function/PA pressure with exercise (ExPH), with the latter phenotype representing a high-risk cohort for progression to resting PAH. In Aim 1, we will institute a protocol of ExMR and CPT that will allow measurement of RV function, mean PA pressure (mPAP) and VO2max in response to exercise to define the prevalence and distinguish patients with abnormal exercise contractile reserve ( RVEF). In aim 2 we will investigate longitudinal changes in resting RV volume, contractile reserve and predictors of progression with a focus on measures of CD8 T cell immune activation and exhaustion and their relationship to progression of PAH. In aim 3, we will follow patients with established or newly diagnosed resting HIV-PAH and evaluate changes in resting RV function, volume and fibrosis and correlate these changes with alteration in invasive hemodynamic parameters at 12 months. We will attempt to delineate the predictors of progression in this patient population. Our proposal is highly responsive to RFA-HL-14-023 and will allow early identification of right heart disease, answer fundamental questions pertaining to cardiopulmonary response with exercise in HIV and lead to appropriately designed outcome trials to prevent PAH and associated functional limitations. (End of Abstract)